PORPHYRIA CUTANEA TARDA

Porphyria cutanea tarda is a common form of porphyria, but is less frequently encountered in South Africa than variegate porphyria. This form of porphyria is unusual in that it is typically an acquired illness, rather than a genetically inherited disorder. It is also the only form of porphyria which is readily treatable.

ENZYME DEFECT

The defective enzyme is uroporphyrinogen decarboxylase. Deficient activity results in the accumulation of large amounts of water-soluble porphyrins (uroporphyrin, hepta-, hexa-, and pentacarboxylic porphyrin, and coproporphyrin). Accumulation of these photoactive porphyrins in the skin results in photosensitivity and skin disease. (See Introduction to porphyria). In the commoner, acquired form, the enzyme activity is diminished as a result of chemical inhibition. In the inherited form, reduced activity results from a mutation in the uroporphyrinogen decarboxylase gene, though the same risk factors as for the acquired form are usually present in clinically expressed cases.

DIAGNOSIS

Porphyria cutanea tarda may be diagnosed by:

• A positive plasma fluorescence peak at 619 nm on plasma fluoroscanning.
• Demonstration of increased concentrations of the uroporphyrin, hepta-, hexa-, and pentacarboxylic porphyrin in urine and plasma on quantitative chromatography.
• Identifying a characteristic porphyrin, isocoproporphyrin, on a stool porphyrin chromatography.

Read this page for more detail: Diagnosis of porphyria.

PRECIPITATING FACTORS

The sporadic form of porphyria cutanea tarda is nearly always accompanied, and apparently precipitated, by some combination of the following factors:

• Hepatic iron overload. This is nearly universal in patients with porphyria cutanea tarda. Recent research has shown that some of these patients have inherited at least one of the common mutations associated with hereditary haemochromatosis, which predisposes them to iron accumulation.
  
  
• Significant alcohol use. A high proportion of patients have a history of significant exposure to alcohol.
  
  
• Oestrogen exposure. Oestrogen exposure, typically as hormone replacement therapy or, in males, for treatment of prostatic carcinoma, is associated with the onset of porphyria cutanea tarda.
  
  
• Chemical toxicity. Porphyria cutanea tarda may also followed exposure to industrial chemicals such as hexachlorobenzene and dioxin.
  
  
• Viral infection. There is a strong association with chronic hepatitis C infection and increasingly, with HIV infection.
  
  
• Hepatitis and liver dysfunction.
  
  
• Other systemic disorders. These include systemic lupus erythematosus and lymphoma.

PATHOGENESIS

The commoner, acquired form of porphyria cutanea tarda appears to result from the reversible inhibition of the enzyme uroporphyrinogen decarboxylase. It appears that, particularly in the presence of iron and chemical compounds such as alcohol, an oxidation process results in the formation of inhibitors. When these factors are removed, the inhibition ceases, enzyme activity returns to normal and the porphyria enters remission. Thus porphyria cutanea tarda is the only truly treatable form of porphyria.

GENE DEFECT

In approximately 20% of cases, porphyria cutanea tarda is inherited as an autosomal dominant trait (See Inheritance of porphyria). Therefore 50% of the children of an affected parent may inherit the disorder. Interestingly, even with the inherited form, most patients will only develop clinically expressed disease after exposure to the same precipitating factors which induce the sporadic form of porphyria cutanea tarda, particularly iron overload and alcohol. Typically however the disease begins at a younger age. This suggests that the defective enzyme is more easily inhibited than the normal enzyme, precipitating the disease more quickly.

CLINICAL EFFECTS

Since only porphyrins, but never the precursors ALA and PBG, accumulate in porphyria cutanea tarda, the disease is never complicated by the acute attack, and skin disease is the only clinical feature. Skin disease takes the form of a typical vesicular-erosive photodermatitis of porphyria, with blisters, sores and scarring in sun-exposed areas. (See Skin disease in porphyria.) This may be very severe, leading to unsightly lesions of the hands, forearms, face and neck, with marked hyperpigmentation and hypertrichosis. Chronic disease may lead to mutilation with thickening and tightening of the skin of the fingers, hands and face which may raise a clinical suspicion of scleroderma: examination however will show that the changes are restricted to sun-exposed areas. Click on the image for examples.

DRUG PRECAUTIONS

Since acute attacks are not encountered in porphyria cutanea tarda, drug precautions are not required. Patients may safely take any drug, though oestrogen should not be prescribed until the disease has been brought into remission.

THERAPY

Management of the patient with porphyria cutanea tarda requires investigation and management of the associated precipitating conditions, such as hepatitis and iron overload, as well as specific therapy. Consult the following for details: Management of porphyria cutanea tarda.